Brain Activity and Oxygenation Inflammatory Bowel Disease (IBD) Patients

NCT04733456 | Unknown

• 1 other identifier: REB20-1873
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Symptoms such as fatigue, sleep disturbances, anxiety and depression are common in patients with IBD, but the cause is unknown. Understanding how these behaviors occur in IBD and their role in symptoms may help improve management of IBD. How IBD leads to changes in brain function remains unclear. Inflammation and dysfunction of blood flow may occur in patients with IBD, which may be linked to these symptoms. Patients with IBD also have an alteration or imbalance of gut bacteria which may play a role in the development of the disease, but the exact mechanism remains poorly understood;as a result, there are limited therapeutic options available clinically to address this issue. An approved therapy, anti-TNF α, may be useful in improving brain and gut activity as well as quality of life. The purpose of this research study is to better understand brain and gut activity in the context of IBD to possibly improve treatments for the disease. In patients taking anti-TNFα therapy as prescribed clinically as standard of care, the investigators will measure brain activity using NIRS; gut microbiome using stool analysis and quality of life using various questionnaires.

Conditions

IBD; Maladaptive Behavior Associated With Physical Illness

Outcome Measures

Primary Outcomes (4)

• a) Clinically: CD (decrease of >3 points in the modified Harvey-Bradshaw Index); UC (decrease of >2 points in the partial Mayo Score)

  Defining differences in alterations of resting state brain NIRS findings occurring in IBD patients, between baseline and at 16 weeks after starting anti-TNF therapy, in anti-TNF responders vs. non-responders, defined: a) Clinically: CD (decrease of \>3 points in the modified Harvey-Bradshaw Index); UC (decrease of \>2 points in the partial Mayo Score)

  16 weeks

• b) Radiographically: decrease in bowel wall thickness ≥25% in most affected segment with 2 point decrease in color Doppler signal score or normalization

  Defining differences in alterations of resting state brain NIRS findings occurring in IBD patients, between baseline and at 16 weeks after starting anti-TNF therapy, in anti-TNF responders vs. non-responders, defined: b) Radiographically: decrease in bowel wall thickness ≥25% in most affected segment with 2 point decrease in color Doppler signal score or normalization

  16 weeks

• c) Biomarker: decrease in fecal calprotectin >50% from baseline or ≤250 ug/g

  Defining differences in alterations of resting state brain NIRS findings occurring in IBD patients, between baseline and at 16 weeks after starting anti-TNF therapy, in anti-TNF responders vs. non-responders, defined: c) Biomarker: decrease in fecal calprotectin \>50% from baseline or ≤250 ug/g

  16 weeks

• d) Endoscopically (where available): CD (decrease in Simple Endoscopic Score for CD ≥50% from baseline); UC (decrease in Mayo endoscopic subscore ≥1 point from baseline)

  Defining differences in alterations of resting state brain NIRS findings occurring in IBD patients, between baseline and at 16 weeks after starting anti-TNF therapy, in anti-TNF responders vs. non-responders, defined: d) Endoscopically (where available): CD (decrease in Simple Endoscopic Score for CD ≥50% from baseline); UC (decrease in Mayo endoscopic subscore ≥1 point from baseline)

  16 weeks

Secondary Outcomes (4)

• (i) alterations in markers of bowel (defined by bowel ultrasound) and systemic inflammation.

  16 weeks

• (ii) reduction from baseline measurement of fecal calprotectin level.

  16 weeks

• (iii) specific gut microbiome and metabolomics signatures.

  16 weeks

• (iv) changes in symptom severity in IBD patients that respond (defined as above), or do not respond to anti-TNF therapy.

  16 weeks

Study Arms (1)

IBD Patients (UC and CD)

Participants will complete a Mayo Clinic Score (UC) or HBI score (CD), short IBDQ73, \*EQ5D-5L, \*GAD-774, \*PHQ-975, \*PROMIS (Gastrointestinal Belly Pain), Multidimensional Assessment of Interoceptive Awareness (MAIA)77, \*Pain Catastrophizing Scale, Pittsburg Sleep Quality Index (PSQI) and Fatigue Severity Scale (FSS) at baseline and 16 weeks after the start of anti-TNF therapy (\*questionnaires available through the CIHR IMAGINE grant). Stool will be collected at baseline and after 16 weeks for assessment of the known biomarker fecal calprotectin, in addition to fecal bacterial and fungal microbiome (through the International Microbiome Center \[IMC\], U of C). Blood will be drawn and urine collected at baseline and after 16 weeks for inflammatory markers and metabolomic \[IMC\] analysis

Behavioral: Quality of life questionnaires; Device: NIRS; Other: Stool Collection; Other: Blood and urine collection

Interventions

Quality of life questionnaires BEHAVIORAL

Mayo Clinic Score (UC) or HBI score (CD), short IBDQ73, \*EQ5D-5L, \*GAD-774, \*PHQ-975, \*PROMIS (Gastrointestinal Belly Pain), Multidimensional Assessment of Interoceptive Awareness (MAIA)77, \*Pain Catastrophizing Scale, Pittsburg Sleep Quality Index (PSQI) and Fatigue Severity Scale (FSS) at baseline and 16 weeks after the start of anti-TNF therapy

IBD Patients (UC and CD)

NIRS DEVICE

A TechEn NIRSOptix continuous-wave fNIRS system will be used to record changes in cerebral oxygenation, at a sampling rate of 25 Hz

IBD Patients (UC and CD)

Stool Collection OTHER

For assessment of the known biomarker fecal calprotectin, in addition to fecal bacterial and fungal microbiome

IBD Patients (UC and CD)

Blood and urine collection OTHER

for inflammatory markers and metabolomic \[IMC\] analysis

IBD Patients (UC and CD)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will have either Ulcerative Colitis or Crohn's Disease

You may qualify if:

• Eligible patients will be:
• \> 18 years of age with moderate-to-severe UC or (partial Mayo score \[excluding endoscopy\] ≥5 with rectal bleeding subscore ≥1; or total Mayo subscore 6-12 with RBS ≥1) or CD (Harvey-Bradshaw index \[HBI\] of 7 or greater, and active CD confirmed on POC bowel ultrasound (defined by bowel wall thickness \>3mm and positive Color doppler signal and a fecal calprotectin \> 50 μg/g ).
• based on their active disease status patients cannot be taking \> 20 mg prednisone daily and
• must be eligible for anti-TNF therapy as per standard of care (clinical decision made by IBD specialist caring for the patient).

You may not qualify if:

• patients with severely active UC (clinical signs of fulminant colitis or toxic megacolon) or CD (HBI \> 16), requiring \> 20 mg of prednisone daily at induction, suicidal ideation or psychosis.

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

RECRUITING

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Biospecimen

Retention: SAMPLES WITHOUT DNA

Urine, stool and blood

MeSH Terms

Interventions

Blood Specimen Collection; Urine Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Mark Swain, MD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark G Swain, MD

CONTACT

403-592-5010; swain@ucalgary.ca

Pam Crotty

CONTACT

403-592-5076; pcrotty@ucalgary.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2020
• First Posted: February 2, 2021
• Study Start: April 26, 2021
• Primary Completion: January 5, 2025
• Study Completion: January 5, 2026
• Last Updated: April 28, 2021

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)